The following description is provided to assist the understanding of the reader. None of the information provided or references cited is admitted to be prior art to the present invention.
Cluster of differentiation (CD) markers have been established to define human leukocyte differentiation antigens (Bernard and Boumsell, Hum Immunol 11(1):1-10, 1984) by the comparison of reactivities of monoclonal antibodies directed against these antigens. These antigens are expressed on the cell surface of leukocytes and, therefore, serve as markers of cell lineage and distinguish populations of leukocytes with different functions, e.g., neutrophils and monocytes.
Leukocyte cell-surface antigens are widely used clinically for the identification of leukocyte populations and their functional status (Krensky et al., Clin Immunol Rev 4(1):244-9, 1985; Kung et al., Int J Dermatol 22(2):67-74, 1983; Cosimi et al., Urol Clin North Am 10(2):289-99, 1983; Knowles et al., Diagn Immunol 1(3):142-9, 1983; and Hoffman et al., Clin Lab Haematol 6(4):383-6, 1984). For example, T cells are typically associated with the expression of specific CD markers such as CD2, CD3, CD5, and CD7, while CD4 and CD8 are associated with helper T cells and cytotoxic cells or suppressor cells, respectively. Similarly, B cells are associated the expression of, for example, CD19 and CD20. Furthermore, many leukemias and lymphomas have been associated with a particular complement of antigen expression on the cell surface of a patient's leukocytes (Rothe et al. Leukemia 10(5):877-95, 1996). This complement of antigens is the CD marker phenotype of that leukocyte and is a basis for identification of the specific leukemia or lymphoma.
CD markers are typically assayed through immunoassays (i.e., assays employing specific antibodies for the detection of antigen). These assays allow the detection of specific antigens based upon the specificity of interaction between a particular antigen and a labeled (e.g., with a fluorescent label) antibody. In general, the specific complement of CD markers expressed on the cell surface of the leukocyte is detected directly using intact leukocytes, labeling the particular CD markers with fluorescently-labeled, marker-specific antibodies and detection using flow cytometry.
It has been recently shown that some CD markers expressed on the surface of leukocytes are circulating free from intact cells in bodily fluids and can be detected by immunoassay. Furthermore, other studies have shown an association between soluble CD markers, as detected by ELISA, and disease staging or monitoring progression (Manshouri T, et al., Blood. 2003 April 1:101 (7):2507-13. Epub 2002 Nov. 21; Heintel D, et al., Leuk. Lymphoma. 2001 November-December; 42(6):1315-21; Foschi F G, et al., Cytokine. 2000 June; 12(6):815-8; Bardin N, et al. Thromb Haemost. 2003 November; 90(5):915-20; Niitsu N, Iijima K., Leuk Res. 2002 March; 26(3):241-8; Albitar M, et al., Cancer. 2004 Sep. 1; 101(5):999-1008; and Hock B D, et al., Cancer. 2003 Oct. 15; 98(8):1681-8), US Patent Publication 2003/0068664, Apr. 10, 2003, and U.S. Pat. No. 5,426,029.